The Barcelona and Real Madrid stars both hit the net within three minutes of each other as the Roja, despite several excellent chances, slumped to yet another defeat
The visitors were let off the hook several times by poor finishing in a brilliant first half, and netted twice in the same period to take another giant leap towards Brazil while Felipe Gutierrez restored some pride for the hosts with his injury-time strike.
Already assured of staying at the CONMEBOL summit come the end of 2012 thanks to Ecuador's draw against Venezuela, Argentina nevertheless came out looking for an instant advantage. A mazy run from Lionel Messi opened the game up for Angel Di Maria on the left, but the midfielder shot wide with time to hit the target. In the opening exchanges, however, it was Chile which set the tempo.
Argentina was under the cosh, but wasted no time in teaching its rival the danger of squandering an early flurry of opportunities. A pinpoint Fernando Gago ball found Messi onside and unmarked; 'La Pulga' released a touch of exquisite simplicity to steady himself, before stroking the ball past Miguel Pinto to net his 31st international goal.
Just seconds later, Chile's woes were doubled. Higuain took the ball wide on the right and ghosted into the box, his left-footed effort giving the keeper no chance and making it 2-0 for the confident visitors.
The rest of the first-half passed in frenetic fashion, as Chile's eagerness to find the net led to as many chances for the Albiceleste as for those in red. Medel had an excellent shout for a penalty after bulldozing his way past two defenders, and then saw his first touch let him down as he hesitated free on the right and allowed Angel Di Maria to make a last-ditch intervention.
At the other end, Sergio Aguero shrugged off the attention of the defense with a wonderful flick, and only a strong save from Pinto forced the ball onto the post to avoid a third. Chile had been more the match of its visitor in Santiago, but nevertheless went into the break trailing by two and with work to do.
The game took on a slightly more sedate pace following the interval, but there were still chances to spare. Federico Fernandez came within inches of connecting with Messi's free-kick and notching the third, while Sebastian Pinto went close for Chile. The striker connected well with Jean Beausejour's cross, but could not steer his effort on goal and missed a fabulous opportunity.
Higuain's withdrawal after suffering a heavy challenge led to the entry of Pablo Guinazu and a more conservative Argentina performance than early on, as it saw out the remaining minutes with minimal fuss. Chile pulled one back in injury time through Felipe Gutierrez, but it was too little too late and the Roja had to watch their neighbors see out a 2-1 win that marks their fourth victory in five World Cup qualifying games over the course of 2012.
The triumph means Argentina enjoys a three-point lead at the top of the South American group, leading Ecuador with 20 while Colombia lies one further back with a game in hand. Chile, meanwhile, is level on points with Venezuela and Uruguay with 12, just outside of the spots guaranteeing a place in Brazil 2014.